Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris

OBJECTIVES: This study was designed to evaluate whether the addition of transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy improves the natural history of unstable angina pectoris. BACKGROUND: Transdermal nitroglycerin is widely used to treat angina pectoris, but the development of tolerance is a major problem that may reduce its clinical efficacy. It has been suggested that the addition of N-acetylcysteine to nitroglycerin reverses the development of tolerance, potentiates the hemodynamic response to nitroglycerin and may improve in-hospital prognosis in unstable angina. METHODS: We assessed the efficacy of adding transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy in a randomized, double-blind, placebo-controlled trial involving 200 patients with unstable angina who were followed up for 4 months. RESULTS: Outcome events--death, myocardial infarction or refractory angina requiring revascularization--occurred in 31% of patients receiving nitroglycerin, 42% of those receiving N-acetylcysteine, 13% of those receiving nitroglycerin plus N-acetylcysteine and 39% of those receiving placebo (p = 0.0052). Kaplan-Meier curves showed a higher probability (p < 0.01) of no failure of medical treatment in the group receiving both nitroglycerin and N-acetylcysteine than in those receiving placebo, N-acetylcysteine or nitroglycerin alone. The combination of nitroglycerin and N-acetylcysteine was associated with a high incidence of side effects (35%), mainly intolerable headache, which was almost twice as frequent as in patients receiving nitroglycerin alone. CONCLUSIONS: The combination of nitroglycerin and N-acetylcysteine, associated with conventional medical therapy in the long-term treatment of patients with unstable angina, reduces the occurrence of outcome events. However, the high incidence of side effects limits the clinical applicability of this therapeutic strategy at least at the dosage used in the present study.     

Late potentials and variability of cardiac frequency in chronic chagasic myocardiopathy and other myocardiopathies

In patients suffering dilated cardiomyopathy, chagasic or not, and in healthy volunteers we applied signal-averaged electrocardiography to detect late potentials and to study heart autonomic control. Thus, with non-invasive methods, we were able to explore the progress of depolarization and heart rate variability. It was found that Chagasic patients have more late potentials and abnormalities in the heart variability; with less co-morbid process when compared with patients suffering miscellaneous cardiomyopathies. These preliminary findings corroborate and expand previous observations by several authors. The signal-averaged electrocardiogram is a valuable tool for clinical diagnosis and research, particularly for studies on dilated cardiomyopathy, specially those with parasitic etiology.     

Detection of Neospora from tissues of experimentally infected rhesus macaques by PCR and specific DNA probe hybridization

Neospora is a newly recognized Toxoplasma-like cyst-forming coccidian parasite that causes abortion or congenital infections in naturally or experimentally infected animals. In this study, pregnant rhesus macaques were inoculated with culture-derived tachyzoites of a bovine Neospora isolate, and tissue samples from various major organs were collected from dams and fetuses for the detection of parasite DNA by using oligonucleotide primers COC-1 and COC-2 for PCR amplification of a conserved coccidial nuclear small-subunit rRNA gene sequence, and amplification products were confirmed by hybridization with a Neospora-specific DNA probe. PCR products were amplified from DNAs of different fetal monkey tissues, including brain, heart, lung, liver, spleen, skeletal muscle, skin, and placenta. In addition, Neospora DNA was amplified from the brain, heart, and lung tissues of infected rhesus macaque dams. The PCR and probe hybridization system may provide an effective method for the detection of Neospora infection in fetuses and dams from nonhuman primates and may be useful in determining the zoonotic potential of Neospora.     

Oral dosing of rats with OM-89 results in the appearance of specific OM-89 antibodies of the IgG2a isotype: possible significance in the treatment of rheumatoid arthritis

OM-89 is a glycoprotein-rich extract of Escherichia coli shown to be effective in the treatment of rheumatoid arthritis (RA). It has been reported that oral dosing of animals results in the appearance of specific OM-89 antibodies. In the current study we have investigated some of the immunoglobulin isotypes that may be involved. OM-89 antibodies of IgG1, IgG2a and IgM isotypes were measured by ELISA in serum from rats dosed three times a week for 3 weeks at 4 or 40 mg kg(-1). The results showed a small but significant rise in IgM and a greater rise in IgG2a. The possibility that antigens within OM-89 (e.g. hsp65) may have homology with antigens involved in RA raises the possibility that OM-89 antibodies, particularly of the IgG2 class, may block pathogenic antigens from being recognized by T cells.     

The glycine site of the NMDA receptor contributes to neurokinin1 receptor agonist facilitation of NMDA receptor agonist-evoked activity in rat dorsal horn neurons

Resistance measurements are the most useful parameters for assessing acute changes in airway caliber associated with bronchodilation or bronchial provocation. Used in addition to spirometry, Raw can provide a better differentiation of the causes of airflow impairment as well as the presence of concurrent processes. A simple, noninvasive Raw measurement can provide definitive answers in the absence of other changes. Finally, the addition of practical, nonplethysmographic measurements opens a new application for bedside, office, and home monitoring.     

New approaches for managing stress incontinence in women

Stress urinary incontinence is a problem for one in four women seen in the primary care setting. The incontinence usually is not identified as women do not view it as a problem, do not seek treatment, and turn to self-care practices. Technology in product development is evolving that can assist women in managing their incontinence. This article reviews new innovations in treatment that can be recommended by primary care providers.     

Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis

Intraperitoneal and intracranial inoculation of herpes simplex virus type 2 (HSV 2) into BALB/cN and C57BL/6N mice was carried out to induce experimental myelitis. The myelitis was clearly observed in C57BL/6N mice following intraperitoneal inoculation. Within 24 hours before death, the mice showed urinary and rectal incontinence and paraplegia of the hind legs. Randomly distributed, severe necrosis was demonstrated in the spinal cord, mainly at the lower cord. In BALB/cN mice the clinical symptoms were not clearly observed, as the mice died shortly after their onset. Although spinal cord necrosis was more prominent in C57BL/6N mice than BALB/cN mice, brain necrosis was only found in the latter, and not in the former. Both strains of mouse showed marked nuclear pyknosis of the nerve cells and slight nuclear pyknosis of the astrocytes in the brain where HSV 2 antigen was demonstrated immunohistochemically. The antigen was also detected in the necrotic spinal cord. In contrast, intracranial inoculation of the virus into both strains did not cause myelitis. Spinal cord necrosis was not demonstrated and virus DNA was not detected, by PCR, in spinal cord samples. In the brain, however, the virus was demonstrated by both PCR and immunohistochemistry.     

Failure to detect intrauterine growth restriction following in utero exposure to MRI

Echo planar imaging is a form of MRI with short image acquisition times, which permits in utero fetal imaging without motion artefacts. Echo planar imaging has been used to measure accurately fetal organ volume and to assess placental function. Two small animal studies have suggested the possibility of intrauterine growth restriction consequent upon MRI. We thus performed a prospective study of pregnancies in which fetuses were exposed to echo planar imaging, compared with a control group in which there was no in utero echo planar imaging exposure. There were no significant differences between the groups when maternal age, parity, proportion of smokers and proportion of Caucasian women were compared. Although the gestational age of delivery was lower in the echo planar imaging group, the proportion of women delivering prematurely was not significantly different. Although infant birthweights were significantly lower in the MRI group, the corrected birthweight for gestational age centiles (individualized birthweight ratio) was not significantly different between the two groups. In utero exposure to echo planar imaging thus did not have a marked effect on intrauterine fetal growth. A 10 year follow-up study of all infants imaged in utero is being performed.     

Pharmacokinetics of the PDGF-antagonist trapidil in patients with and without renal impairment

BACKGROUND: From July 1989 to February 1996, 130 patients underwent stereotactic radiosurgery. We report the results of the first 50 patients eligible for a minimum of three years of follow-up. METHODS: Twenty women and 30 men, (mean age: 37.5 years) were treated by dynamic rotation on a 6 MV linear accelerator. Prior treatment was embolization in seventeen, surgery in three and embolization and surgery in six. All had DSA and enhanced CT scanning, while some had MRI. Forty-seven treatments used a single isodose. Restricting eloquent normal tissue to 15 Gy, margin doses (at 50-90% isodose) were 12 Gy (one patient); 15 Gy (sixteen patients); 20 Gy (31 patients); 25 Gy (two patients). Maximum diameters were: < 1.5 cm (12 patients); < 2.0 cm (nine patients); < 2.5 cm (twelve patients); < 3.0 cm (thirteen patients; 3.0 cm (four patients). RESULTS: Forty-five patients were evaluable at three years, with thirty-nine having angiography. Twenty-five had angiographically confirmed obliterations; two had parenchymal AVMs obliterated but with residual dural components; four had MRI evidence of obliteration (refused angiography). One patient acutely had a seizure; one patient (with hemorrhages, resection, and embolizations preceding two applications of radiosurgery, separated by 3.5 years) had worsening of memory. CONCLUSIONS: Our uncorrected (five patients unevaluable at three years) and corrected angiographically confirmed obliteration rates are 54% and 60% respectively. Our follow-up (98% accounting of cohort; 78% angiographic rate) and explicit derivation of denominators help delineate the efficacy of radiosurgery at these doses.